Project Title
Treating the whole not the hole: Administration of acellular derivative from mesenchymal stem cells subjected to a preconditioning stimulus reverts diabetic neuropathy and prevents diabetic foot ulcers in an animal model of type 2 diabetes mellitus
Partner Organisations
Internal ID
1170712
Principal Investigator
Type
basic research
Status
TERMINADO
Start Date
2017
Investigators
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Item type:Publication, Sensory neuron cultures derived from adult db/db mice as a simplified model to study type-2 diabetes-associated axonal regeneration defects<jats:title>ABSTRACT</jats:title> <jats:p>Diabetic neuropathy (DN) is an early common complication of diabetes mellitus (DM), leading to chronic pain, sensory loss and muscle atrophy. Owing to its multifactorial etiology, neuron in vitro cultures have been proposed as simplified systems for DN studies. However, the most used models currently available do not recreate the chronic and systemic damage suffered by peripheral neurons of type-2 DM (T2DM) individuals. Here, we cultured neurons derived from dorsal root ganglia from 6-month-old diabetic db/db-mice, and evaluated their morphology by the Sholl method as an easy-to-analyze readout of neuronal function. We showed that neurons obtained from diabetic mice exhibited neuritic regeneration defects in basal culture conditions, compared to neurons from non-diabetic mice. Next, we evaluated the morphological response to common neuritogenic factors, including nerve growth factor NGF and Laminin-1 (also called Laminin-111). Neurons derived from diabetic mice exhibited reduced regenerative responses to these factors compared to neurons from non-diabetic mice. Finally, we analyzed the neuronal response to a putative DN therapy based on the secretome of mesenchymal stem cells (MSC). Neurons from diabetic mice treated with the MSC secretome displayed a significant improvement in neuritic regeneration, but still reduced when compared to neurons derived from non-diabetic mice. This in vitro model recapitulates many alterations observed in sensory neurons of T2DM individuals, suggesting the possibility of studying neuronal functions without the need of adding additional toxic factors to culture plates. This model may be useful for evaluating intrinsic neuronal responses in a cell-autonomous manner, and as a throughput screening for the pre-evaluation of new therapies for DN.</jats:p>2 1Scopus© Citations 3 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Intravenous administration of anti-inflammatory mesenchymal stem cell spheroids reduces chronic alcohol intake and abolishes binge-drinking(2018); 1Scopus© Citations 43 1 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Characterization of diabetic neuropathy progression in a mouse model of type 2 diabetes mellitus(2018); ; ; <jats:p>Diabetes mellitus (DM) is one of most frequent chronic diseases with an increasing incidence in most countries. Diabetic neuropathy (DN) is one of the earliest and main complications of diabetic patients, which is characterized by progressive, distal-to-proximal degeneration of peripheral nerves. The cellular and molecular mechanisms that trigger DN are highly complex, heterogeneous and not completely known. Animal models have constituted a valuable tool for understanding diabetes pathophysiology; however, the temporal course of DN progression in animal models of type 2 diabetes (T2DM) is not completely understood.</jats:p> <jats:p>In this work, we characterized the onset and progression of DN in BKS db/db mice, including the main functional and histological features observed in the human disease. We demonstrated that diabetic animals display a progressive sensory loss and electrophysiological impairments in early-to-mid phases of disease. Furthermore, we detected an early decrease in intraepidermal nerve fibers (IENF) density in 18-week-old diabetic mice, which is highly associated with sensory loss and constitutes a reliable marker of DN. Other common histological parameters of DN, like Schwann cells apoptosis and infiltration of CD3+ cells in the sciatic nerve, were altered in mid-to-late phases of disease.</jats:p> <jats:p>Our results support the general consensus that DN evolves from initial functional to late structural changes. This work aimed to characterize the progression of DN in a reliable animal model sharing the main human disease features, which is necessary to assess new therapies for this complex disease. Finally, we also aimed to identify an effective temporal window where these potential treatments could be successfully applied.</jats:p>6 1Scopus© Citations 43 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Activated mesenchymal stem cell administration inhibits chronic alcohol drinking and suppresses relapse-like drinking in high-alcohol drinker rats(2019); ; Carolyne Lespay-Rebolledo1Scopus© Citations 31 2 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Gene and cell therapy on the acquisition and relapse-like binge drinking in a model of alcoholism: translational options(2019)26Scopus© Citations 4 - Some of the metrics are blocked by yourconsent settings
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Item type:Publication, Neonatal Mesenchymal Stem Cell Treatment Improves Myelination Impaired by Global Perinatal Asphyxia in Rats(2021)Scopus© Citations 7 2 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, Intranasal delivery of mesenchymal stem cell-derived exosomes reduces oxidative stress and markedly inhibits ethanol consumption and post-deprivation relapse drinking(2019); 1Scopus© Citations 60 5 - Some of the metrics are blocked by yourconsent settings
Item type:Publication, 6Scopus© Citations 126